Hepatic steatosis, or fatty liver, results from an imbalance between production and removal of hepatic triglycerides (TAGs) (Cohen et al., 2011). This imbalance can result from excessive alcohol consumption (alcoholic fatty liver disease) or through other means (non-alcoholic fatty liver disease, NAFLD). In NAFLD, elevated hepatic TAG (triacylglycerol) is caused by a combination of excess dietary lipids and de novo fatty acid synthesis (Cohen et al., 2011; Browning and Horton, 2004; Postic and Girard, 2008). Fat oxidation and TAG export (in the form of very low-density lipoprotein, VLDL) aid in removal of hepatic TAGs. NAFLD is one of the primary causes of abnormal liver function (Cohen et al., 2011), frequently linked to hepatic insulin resistance and uncontrolled gluconeogenesis in the diabetic state (Browning and Horton, 2004; Kotronen et al., 2008; Kotronen et al., 2007; Sunny et al., 2011; Jornayvaz et al., 2011; Kim et al., 2001). Indeed, up to 70% of clinically obese patients have NAFLD (Luyckx et al., 1998). Further, obese patients with NAFLD are at a significantly higher risk of developing obesity-associated co-morbidities (e.g., heart disease and type 2 diabetes) (Treeprasertsuk et al., 2012). For reasons still poorly understood, a subset of patients with NAFLD will go on to develop NASH (nonalchoholic steatohepatitis) and cirrhosis (Cohen et al., 2011). Despite the prevalence of NAFLD in the general population (Lazo and Clark, 2008; Szczepaniak et al., 2005), therapeutic options are limited.
CTRP3 (Clq/TNF-related protein) is a secreted plasma protein of the Clq family that helps regulate hepatic gluconeogenesis and is down-regulated in a diet-induced obese state. However, the role of CTRP3 in regulating lipid metabolism has not been established.